The first two authors contributed equally.
New therapeutic targets in ulcerative colitis: The importance of ion transporters in the human colon
Article first published online: 18 AUG 2010
Copyright © 2010 Crohn's & Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 17, Issue 4, pages 884–898, April 2011
How to Cite
Farkas, K., Yeruva, S., Rakonczay, Z., Ludolph, L., Molnár, T., Nagy, F., Szepes, Z., Schnúr, A., Wittmann, T., Hubricht, J., Riederer, B., Venglovecz, V., Lázár, G., Király, M., Zsembery, Á., Varga, G., Seidler, U. and Hegyi, P. (2011), New therapeutic targets in ulcerative colitis: The importance of ion transporters in the human colon. Inflamm Bowel Dis, 17: 884–898. doi: 10.1002/ibd.21432
- Issue published online: 9 MAR 2011
- Article first published online: 18 AUG 2010
- Manuscript Accepted: 22 JUN 2010
- Manuscript Received: 16 JUN 2010
- OTKA. Grant Numbers: CK 80136, NNF 78851, K79189
- NKTH. Grant Numbers: TÁMOP-4.2.2-08/1/2008-0002, 0013
- MTA. Grant Numbers: Bolyai BO/00334/08/5, BO/00174/10/5
- Deutsche Forschungsgemeinschaft DFG. Grant Numbers: Se 460/13-4, SFB621-C9
- DAAD and Abbot GmbH, Wiesbaden, Germany
- ulcerative colitis;
- therapeutic targets;
- ion transporters
The absorption of water and ions (especially Na+ and Cl−) is an important function of colonic epithelial cells in both physiological and pathophysiological conditions. Despite the comprehensive animal studies, there are only scarce available data on the ion transporter activities of the normal and inflamed human colon.
In this study, 128 healthy controls and 69 patients suffering from ulcerative colitis (UC) were involved. We investigated the expressional and functional characteristics of the Na+/H+ exchangers (NHE) 1–3, the epithelial sodium channel (ENaC), and the SLC26A3 Cl−/HCO exchanger downregulated in adenoma (DRA) in primary colonic crypts isolated from human biopsy and surgical samples using microfluorometry, patch clamp, and real-time reverse-transcription polymerase chain reaction (RT-PCR) techniques.
Data collected from colonic crypts showed that the activities of electroneutral (via NHE3) and the electrogenic Na+ absorption (via ENaC) are in inverse ratio to each other in the proximal and distal colon. We found no significant differences in the activity of NHE2 in different segments of the colon. Surface cell Cl−/HCO exchange is more active in the distal part of the colon. Importantly, both sodium and chloride absorptions are damaged in UC, whereas NHE1, which has been shown to promote immune response, is upregulated by 6-fold.
These results open up new therapeutic targets in UC. (Inflamm Bowel Dis 2011;)